2012 Updates on Management of Contrast Induced AKI —— Guidelines & New Evidences Prof. Ben He MD PhD FACC Shanghai Renji Hospital Shanghai Jiaotong University （上海交通大学医学院附属仁济医院 何奔）

Epidemiology: Incidence of CI-AKI A survey in Shanghai China.2010 Data from US Am J Cardiol 2004;93:1515–1519 Without Significant Reduction in Past Decade

Prognosis: Circulation. 2012;125: Death MACE+DIALYSIS Poor prognosis, especial for pts with persistent renal damage

5 Mechanisms: Direct cytotoxic effects Renal haemodynamics Renal tubulodynamics Regional hypoxia European Heart Journal (2012) 33, 2007– Key Factors:

Important Updates on CI-AKI Guidelines New Researches

I. Definition Traditional Definition of CI-AKI An increase in SCr by more than 25% or 44 μmol/L in the 3 days following intravascular administration of contrast medium (CM) in the absence of an alternative etiology. Other Definition of CI-AKI An increase in CysC by more than 10% in the 24h following intravascular administration of contrast medium (CM).

New Definition: I. Definition Stage 1: SCr increased 1.5–1.9 times baseline SCr increase >0.3mg/dl (26.5 μmol/l) Urinary output < 0.5ml/kg/h during a 6 hour block Stage 2: SCr increase 2.0–2.9 times baseline Urinary output <0.5ml/kg/h during two 6 hour blocks Stage 3: SCr increase >3 times baseline SCr increases to >4.0mg/dl (353 μmol/l) Initiation of renal replacement therapy Urinary output <0.3ml/kg/h during more than 24 hours Anuria for more than 12 hours

New criterior increase sen and sep ? Am Heart J 2012;163: Which definition is better? We need further studies!

Balancing the risk for CIN against the benefit of administering contrast. (Not Graded) Considering alternative imaging methods not requiring contrast administration in patients at increased risk for CIN, so long as these yield the same diagnostic accuracy. (Not Graded) II. Risks Assessment 2011 PCI guideline

11 Mehran Score is proved to predict long-term outcomes. J Am Coll Cardiol.2004;44:1393–9 Clin. Cardiol. 2013,36, 1, 46–53 Predicting Score: Traditional Methods

Easy for practice Baseline Kidney Function Screening—— MDRD formula is preferred

2011 PCI guideline 3.7

2011 PCI guideline 2.62 Data from China Lower than Western Countries ！

New Simple Algorithm: To stratify the risk of CI-AKI Maximum Allowable Contrast dose (MACD) was defined as 5*body weight/SCr Increases the positive predictive value of the Mehran risk score (40.7% vs 8.8%) with the same sensitivity (90.7% vs 83.3%) Catheterization and Cardiovascular Interventions,2013, doi: /ccd.24847

Better Contrast Media: Low- Osmolar vs. Iso- Osmolar CM Data from Chinese Population EuroIntervention 2012;8: PCI guideline 2011 UA/NSTEMI guideline

CKD+DM CKD —— No Difference! EuroIntervention 2012;8:

Among Low- Osmolar CMs: Iohexol vs. Iopamidol vs. Ioversol : No apparent clinical advantage among LOCM agents. Am J Cardiol 2012;109:1594–1599

New Factors Rising Concerns: ACEI or ARB increase the risk of CI-AKI? Am J Kidney Dis. 60(4): Further RCTs are warranted ! Retrospective Study

III. Pharmacological Prevention Volume expansion with either isotonic NS or SB (1A) Oral route for hydration, on the premise that adequate intake of fluid and salt are assured (2C) Oral N-acetyl cysteine (NAC) only in appropriate fluid and salt loading (2D). Not using oral NAC as the only method (1D) Do not suggest using theophylline (2C) Do not recommend using fenoldopam (1B) 2011 PCI guideline

Optimal Hydration Protocol: (A) NS 1 mL/kg/h for at least 12 h prior and after the procedure (B) SB 3 mL/kg for 1 h before and 1 mL/kg/h for 6 h after the procedure (C) SB 3 mL/kg over 20 min before the procedure plus sodium bicarbonate orally (500 mg per 10 kg). European Heart Journal (2012) 33, 2071–2079

22 24 h sodium chloride 0.9% is superior to sodium bicarbonate. A short-term regimen with sodium bicarbonate is non-inferior to a 7 h regimen. Optimal Hydration Protocol: European Heart Journal (2012) 33, 2071–2079

Precise Hydration Renal-Guard System: capable of delivering sterile replacement solution in an amount matched to the volume of urine, avoiding hypovolemia and fluid overload. J Am Coll Cardiol Intv 2012;5:90 –7

Benefit for pts with CKD ! J Am Coll Cardiol Intv 2012;5:90 –7 Pilot RCT with 170 pts

New hydration agent: Promising Results! European Heart Journal doi: /eurheartj/eht009 RCT

2011 UA/NSTEMI guideline 2308pts were randomized to NAC group or placebo New Evidence ： ACT trial HR, 0.97; 95% CI, ; P=0.92 NAC: ineffective!

High Dose Statin——no yet accepted by guidelines Meta analysis shows ： high dose statin might be effective

New Evidence ： ARMYDA-CIN trial NSTEMI patients : totally 120mg atorvastatin within 12 hours prior to PCI Endpoint ： CIN% 阿托伐他汀安慰剂组 对比剂肾病发生率 (%) P= Giuseppe Patti, et al. Am J Cardiol, 2011 online Perioperative high-dose statin load to reduce perioperative myocardial infarction has been recognized; Prevention of CIN may be derived from the pleiotropic effects of statins.

29 Circulation. 2005;111: Worry Some - Rosuvastatin Increase the risk of inducing proteinuria and renal function injury - CIN? TRACK-D trial: to eliminate this concern Han YL et al CIT meeting report.

IV. Renal Replacement Therapy Do not recommend using prophylactic intermittent haemodialysis (IHD) or haemofiltration (HF) for the purpose of prevention of CIN only. (1C)

New Evidence : Meta-analysis Risk of CI-AKI: No benefit, Even increase the risk! Among the CKD stage Support current guideline! The American Journal of Medicine Volume 125, Issue 1, January 2012, Pages 66–78.e3

V. Beyond guidelines Protocol: IPC was accomplished by performing 4 cycles of alternating 5-minute inflation and 5-minute deflation of a standard upper-arm blood pressure cuff to the individual’s systolic blood pressure plus 50 mm Hg to induce transient and repetitive arm ischemia and reperfusion. Circulation. 2012;126: Pros:

Ischemic Preconditioning A Pilot RCT Simple procedure but maybe effect!

Precise CM volume injection Automated Contrast Injection Systems Incidence of CI-AKI 9% vs 9% P=0.84 Canadian Journal of Cardiology 29 (2013) No Benefit ! Cons: 1358 pts undergoing CAG and PCI from January 31 to May 31, 2011 Manual vs Automated injection

Summary: Something We Gain A Lot We Still Unknown!

Thank You !